In treating certain unhealthy conditions, including several categories of severe illness, it is highly desirable to localize or target delivery of a therapeutic to a tissue or organ in need of treatment. This is so for three main reasons. One reason is that the therapeutic has toxic and/or adverse side effect(s) and systemic delivery is deleterious; e.g., this is particularly the case with chemotherapy. The second reason is that the therapeutic is very expensive; e.g., this is particularly the case with biologics. The third reason is that effective treatment requires a high dosage.
It is known in the art to localize or target the delivering of a therapeutic by linking the therapeutic to an antibody and/or ligand for a cell surface receptor. This technology has the disadvantages of a lack of specificity of the monoclonal antibody or ligand to exclusively target a tissue or organ, a micro environment surrounding the tissue or organ that restricts or inhibits access by the antibody or ligand linked therapeutic and an adverse immune response to the antibody or ligand linked therapeutic.
Changing the subject to a different aspect of the delivery of a therapeutic, there is often in pharmacokinetics a time-dose relationship in order to achieve a desired therapeutic effect. Hence, controlled elution devices have been developed that provide for the time extended delivery of some therapeutics. Notwithstanding, there exist a wide range of therapeutics for which time extended delivery by current means is not possible or for which a limited time-dose delivery can be achieved which in turn limits effectiveness or results in side effects.
It is known in the art to construct controlled elution devices using parylene C and other derivatives of parylene. Parylene C is a USP class VI biocompatible material and is certified nontoxic. The atomic composition of Parylene C is a carbon, hydrogen and chlorine. The chemical structure is a chain of chlorinated xylenes. That is, methylated benzene ring with a chlorine atom on the benzene ring that are connected by their methyl groups such that the methyl groups serve as connecting bridges.
A review of what was known in the art as of 2005 is presented in L. Wolgemuth., “A Look at Parylene Coatings in Drug-Eluting Technologies,” Medical Device & Diagnostic Industry Magazine, (August, 2005.) Wolgemuth wrote that “Manufacturers can also manipulate the thickness of the coating [of parylene] to very thin, porous layers and vary the ratio of drug to parylene in a multiple-layer construct. These attributes enable it to provide control of the drug-delivery rate. The parylene coating can be applied over the drug-coated stent surfaces (drug application is not a part of the vapor-deposition polymerization process) in layers sufficiently thin such that its matrix structure becomes open and porous. At these angstrom thickness levels, parylene allows drug molecules to pass through it at a rate that is a function of film thickness and drug molecule size. [paragraph] In a multilayer device, for example, a drug-to-carrier polymer ratio that is higher in the interior layers than in the external layers could result in a lower initial dose delivery and in a total dose that would be delivered more uniformly and over a sustained period.” This technology has the disadvantages of not being directed at a standalone capable device, not overcoming failures that occur in a coating that is flexible and undergoes deformation, not being tunable to achieve particular elution profiles, lacking accuracy and not accommodating a wide spectrum of therapeutics.
Known in the art is a parylene based controlled elution device in connection with a medical device (namely, a stent) as taught by U.S. Pat. No. 7,445,628 B2 by Ragheb et al. assigned to Cook Incorporated and US Patent Application Publication US2007/0150047 A1 by Ruane et al. assigned to Cook Incorporated (hereafter collectively “Cook.”) These patents disclose a first coating layer of parylene posited on the stent. On at least a portion of this coated structure, there is a layer comprising a bioactive; namely, an immunosurpressive agent or paclitaxel. Overlying this layer, there is a porous layer of a parylene derivative in a thickness between 5,000 to 250,000 Angstroms (i.e., 5×10-7 meters to 2.5×10-5 meters; 0.5 to 25 microns or 500 to 25,000 nanometers.) The teaching of Cook has the disadvantage of not being directed at a standalone capable device, not overcoming failures that occur in a coating that is flexible and undergoes deformation, not being tunable to achieve particular elution profiles, lacking accuracy and not accommodating a wide spectrum of therapeutics.
Known in the art is a parylene based controlled elution device in connection with a medical device (namely, a stent) as taught by US Patent Application Publication US2005/0033414 A1 by Zhang et al. and assigned to Microport Medical Co., Ltd. and US Patent Application Publication US2005/0043788 A1 by Luo et al. and assigned to Microport Medical Co., Ltd. (hereafter collectively “Microport.”) These patents disclose a stent is coated with a primer. There are one or more overlying drug layers. On top of the drug layer(s) is coated a controlled releasing barrier layer. The thickness of the entire coating is between 0.1 to 100 microns. There is a discloser of data for the release rates of different molecular weight drugs (Cilostazol and Rapamycin) where the controlled releasing barrier layer is parylene. There is a disclosure of data for the release rates of camptothecin where the controlled releasing barrier layer is a parylene coating having a thickness that is 0.05 microns, 0.1 microns, 0.2 microns, 0.4 microns or 0.5 microns. The teaching of Microport has the disadvantage of not being directed at a standalone capable device, not overcoming failures that occur in a coating that is flexible and undergoes deformation, not being tunable to achieve particular elution profiles, lacking accuracy and not accommodating a wide spectrum of therapeutics.
A deficiency in the art is a standalone controlled elution device (not supported by a medical device) that is flexible, resistant to tearing and resistant to delamination. Another deficiency in the art is a mechanism for the time extended delivery that is suitable for a broad spectrum of therapeutics or combination of therapeutics. Another deficiency in the art is a mechanism for accurately controlling the time extended delivery of certain therapeutics or combination of therapeutics. Another deficiency in the art is a tunable parylene controlled elution device to achieve certain needed elution profiles.
There exists a need for standalone controlled elution device in a usable size that is flexible and can undergo deformation without significant delamination and/or tearing. There is a sub-need for a controlled elution that is standalone capable that can be disposed in vivo on an organ or tissue for the localized and/or targeted delivery of a therapeutic.
There exists a need for a controlled elution device for certain therapeutics or combination of therapeutics for which current devices are not capable of delivering extended release in a clinically meaningful way. There is a particularized sub-need for controlled elution devices to deliver hormone replacement or adjunct therapy.
There exists a need for a controlled elution device that is tunable to achieve a particular elution profiles that have heretofore been unachievable in a clinically meaningful way.
There exists a need for a controlled elution device that more accurately and/or with greater control delivers a therapeutic or combination of therapeutics.
There exists a need for a controlled elution device that is simplified with no overlying barrier layer.
There exists a need for solutions to the above deficiencies in the art that are cost effective in the market for healthcare.
The present invention satisfies these needs, as well as others, and generally overcomes the presently known deficiencies in the art.